Hadar Goldvaser1, Domen Ribnikar2, Habeeb Majeed3, Alberto Ocaña4, Eitan Amir5. 1. Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G 2M9, Canada; Sackler Faculty of Medicine, Tel Aviv University, POB 39040, Tel Aviv 6997801, Israel. 2. Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G 2M9, Canada. Electronic address: domen.ribnikar@uhn.ca. 3. Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G 2M9, Canada. Electronic address: habeeb.majeed@uhn.ca. 4. Translational Research Unit, Centro Regional de Investigaciones Biomedicas Universidad de Castilla La Mancha, Albacete University Hospital, calle Francisco Javier de Moya, 02006 Albacete, Spain. 5. Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G 2M9, Canada. Electronic address: eitan.amir@uhn.ca.
Abstract
BACKGROUND: Many adjuvant breast cancer trials have observed smaller than anticipated differences between experimental and control groups. Accurate estimation of the absolute benefits of treatment is essential for the planning of clinical trials. METHODS: We searched PubMed to identify contemporary randomized trials comparing different adjuvant chemotherapy regimens in breast cancer. The absolute difference in 5-year disease-free survival (DFS) and overall-survival between experimental and control groups were extracted, weighted by individual study sample size and pooled. Analyses were performed for estrogen receptor (ER) negative and ER-positive disease. Meta-regression explored the influence of patients and tumor characteristics and median follow-up on the benefit from treatment. RESULTS: Analysis included 19 studies comprising 41,564 patients. Studies comparing chemotherapy regimens of different generations showed the largest difference in 5-year DFS (+7.4% for 3rd vs. 2nd generation and +5.9% for 2nd vs. 1st generation for ER-negative disease, and +2.3% for 3rd vs. 2nd generation and +1.8% for 2nd vs. 1st generation for ER-positive disease). Studies comparing chemotherapy regimens from the same generation showed smaller differences in DFS in both subgroups. Meta-regression showed that larger tumors and nodal involvement had significant greater magnitude of effect on 5-year DFS for ER-negative, but not ER-positive disease. Age and menopausal status had no effect in either subgroup. CONCLUSIONS: Absolute differences between adjuvant chemotherapy regimens of the same generation are small even in ER-negative disease. Enrichment of trials for patients with poor clinical features results in larger magnitudes of benefit from treatment at 5 years in ER-negative, but not ER-positive disease.
BACKGROUND: Many adjuvant breast cancer trials have observed smaller than anticipated differences between experimental and control groups. Accurate estimation of the absolute benefits of treatment is essential for the planning of clinical trials. METHODS: We searched PubMed to identify contemporary randomized trials comparing different adjuvant chemotherapy regimens in breast cancer. The absolute difference in 5-year disease-free survival (DFS) and overall-survival between experimental and control groups were extracted, weighted by individual study sample size and pooled. Analyses were performed for estrogen receptor (ER) negative and ER-positive disease. Meta-regression explored the influence of patients and tumor characteristics and median follow-up on the benefit from treatment. RESULTS: Analysis included 19 studies comprising 41,564 patients. Studies comparing chemotherapy regimens of different generations showed the largest difference in 5-year DFS (+7.4% for 3rd vs. 2nd generation and +5.9% for 2nd vs. 1st generation for ER-negative disease, and +2.3% for 3rd vs. 2nd generation and +1.8% for 2nd vs. 1st generation for ER-positive disease). Studies comparing chemotherapy regimens from the same generation showed smaller differences in DFS in both subgroups. Meta-regression showed that larger tumors and nodal involvement had significant greater magnitude of effect on 5-year DFS for ER-negative, but not ER-positive disease. Age and menopausal status had no effect in either subgroup. CONCLUSIONS: Absolute differences between adjuvant chemotherapy regimens of the same generation are small even in ER-negative disease. Enrichment of trials for patients with poor clinical features results in larger magnitudes of benefit from treatment at 5 years in ER-negative, but not ER-positive disease.
Authors: L M McSorley; M Tharmabala; F Al Rahbi; K McSorley; S Chew; D Evoy; J G Geraghty; R S Prichard; J Rothwell; D P McCartan; E W McDermott; M Keane; M J Kennedy; S O'Reilly; S J Millen; J P Crown; L M Smyth; C M Kelly; C M Quinn; J M Walshe Journal: Breast Cancer Res Treat Date: 2021-04-09 Impact factor: 4.872
Authors: Manpreet Sambi; Vanessa Samuel; Bessi Qorri; Sabah Haq; Sergey V Burov; Elena Markvicheva; William Harless; Myron R Szewczuk Journal: Drug Des Devel Ther Date: 2020-05-25 Impact factor: 4.162
Authors: Daniel A Goldstein; Chen Mayer; Tzippy Shochat; Daniel Reinhorn; Assaf Moore; Michal Sarfaty; Rinat Yerushalmi; Hadar Goldvaser Journal: Cancer Med Date: 2020-05-06 Impact factor: 4.452